Mammographically dense breast tissue has been recognized as a strong risk factor for breast cancer, conferring a 4-6 fold increased risk for those women with the most dense compared with those with the least dense breast tissue. Thus, it identifies a group of women in whom the benefits of chemoprevention, more frequent screening, and/or screening by alternative methods may outweigh the associated risks and expense. However, the biological basis of the increased risk for breast cancer in women with mammographically dense breast is unknown. Knowledge of the underlying mechanism will inform more rational prevention strategies. The goal of the proposed research is to better characterize the biological basis for and prognostic importance of mammographic density as a risk factor for development of invasive breast cancer. Specifically, we will explore the relationship of mammographic density with histologic findings on breast biopsy and with serum insulin-like growth factor-1 (IGF-1) bioavailability. This study will be carried out by performing quantitative assessment of mammographic density and measuring IGF-1 and insulin-like growth factor binding protein-3 in 550 women who are undergoing breast biopsy due to mammographic and/or physical examination abnormalities and participating in an ongoing biomarker discovery study, for which Dr. Edith A. Perez (mentor) is the principal investigator and Dr. Betty A. Mincey (candidate) is a co-investigator. The purpose of this ongoing study is to identify and validate potential serum markers for the presence of breast cancer, using proteomic and genomic techniques. The study proposed herein capitalizes on the opportunity provided by this ongoing biomarker trial and will provide a foundation for future research into the relationship of mammographic density, histological diagnoses, IGF-1 bioavailability, and new predictive biomarkers for breast cancer. The candidate, Dr. Betty A. Mincey, is an internist who has developed expertise in the area of cancer prevention, with special interest in assessment and management of women at high risk for breast cancer. Dr. Mincey's clinical practice is centered in the Breast Clinic at Mayo Clinic in Jacksonville, Florida. She has worked closely with her mentorship team to develop a career development plan that, along with the work outlined in this research proposal, will enable her to develop into an independent clinical investigator in the field of breast cancer prevention.